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Biomedical subjects

E Boschetti

Publications and source records attributed to E Boschetti.

At least 73 records · Page 4Linked to original sources

[Isolation of human thrombin by affinity chromatography with silicate to be used in the preparation of biological glue].

At present the preparations of fibrin glue used a thrombin from equine or bovine origin. In order to remove the problems of antigenicity we developed a method of purification from acidified plasma. We used one affinity chromatography on benzamidine-Spherodex and compared three methods of elution: non specific (sodium chloride gradient) and biospecific competitors (arginin methylester or benzamidin). The yield is evaluated between 64 and 84% and the purification factor close to 160. The obtained thrombin is better than animal thrombin in the preparations of fibrin glue.

Benzamidines↗

Pharmacokinetics of vincristine in cancer patients treated with nifedipine.

The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated.

Aged↗

Polyacrylamide derivatives to the service of bioseparations.

Though acrylamide polymers are widely used in electrophoretic and chromatographic techniques, many research works aim at optimizing these media. As polyacrylamide presents some drawbacks, new acrylic monomers with particular properties are proposed. In this paper, we describe some approaches for obtaining polymers which are more porous, more hydrophilic and more resistant in alkaline solutions. Moreover, we also detail the synthesis of particular functionalized monomers, explaining the concept of 'polymer design' applicable to the techniques of protein separation.

Acrylic Resins↗

[Purification of human thrombin by affinity chromatography for its use in preparations for biological coagulation].

Biological glue is obtained by mixing different specific plasma proteins including a serine protease, thrombin. Surprisingly at present the thrombin used in such a mixture is from equine or bovine origin while all other components are from human. In this paper we described a particular efficient and specific chromatographic method for the purification of human thrombin usable as a serine protease in the preparation of biological glue. A pure and active thrombin is obtained from a plasma fraction after adsorption on benzamidine-Spherodex followed by an elution with non specific (sodium chloride gradient) or biospecific competitors (arginine methylester or benzamidine). The obtained thrombin with a yield close to 80% and a purification factor close to 160, showed good properties in the replacement of animal thrombin in the condition of biological glue.

Benzamidines↗

[Optimization of the purification of human plasma fibronectin by double affinity chromatography using gelatin and heparin Trisacryl LS].

The authors described an optimized method of preparation to obtain pure human plasma fibronectin. The new performances related to the chromatographic and concentration steps, where the saving of time is about 40% and the lyophilization step where the saving of energy is also about 40%. The final product is without any less of either physical and biological activities. The size of the columns, the volumes of the chromatographic supports (gelatin and heparin-Trisacryl LS) and the quantity of the treated plasma are very much important and also the quantities of the final product are very increased.

Acrylic Resins↗

Round table on antiasthmatic drugs; beta-agonists and theophylline. Workshop on pathogenesis and therapy of bronchial asthma Cortina d'Ampezzo/1-4 April, 1987.

Beta 2-agonists and theophylline compounds are first line drugs and are extensively used in the treatment of acute bronchial asthma. Beta 2-agonists are continuously expanding as a class of drugs. Recent research has increased the available knowledge of their cardiovascular and metabolic effects. Cardiovascular effects might be due to direct stimulation of beta 2-receptors sited in the atrial muscle. Metabolic effects (i.e. increase in blood glucose, insulin and non-esterified fatty acid (NEFA), decrease in plasma potassium) are, at least partly, a consequence of direct or reflex stimulation. Despite recent progress, slow-release theophylline compounds remain a basic approach to asthma management. Future progress in this field will probably be concerned with a more complete knowledge of 'ultra-slow' theophylline compounds (level of the plasma concentration fluctuation and patient compliance) and more complete results regarding the influence exerted by food (and gastric pH) on the rate and extent of absorption.

Adrenergic beta-Agonists↗

p-Benzylthiocarbamoyl-aspartyl-daunorubicin-substituted polytrisacryl. A new drug acid-labile arm-carrier conjugate.

A new type of drug acid-labile arm-carrier is described. A hydrophilic polymer [polytrisacryl, or poly(acryloyl 2-amido-2-hydroxymethyl-1,3-propanediol)], used as a model, is substituted with p-nitrobenzyl groups. The nitrobenzyl groups are reduced to aminobenzyl and transformed into benzylisothiocyanate groups which are allowed to react with aminoacyl daunorubicin. The excess of benzylisothiocyanate is transformed into benzylthiocarbamoyl N-methyl glucamine. A conjugate containing benzylthiocarbamoyl-aspartyl daunorubicin is stable at neutral pH, and releases free daunorubicin when it is exposed to pH 5 or below. This conjugate is about 200-fold less toxic than free daunorubicin, on a molecular basis, when it is added to the medium of Lewis lung carcinoma (3LL) cells in culture.

Acrylates↗

Application of chromatographic methods to the analysis of macrophage factors induced by Nocardia opaca cell walls.

Cell walls from Nocardia opaca induce the production of mitogenic factors by mouse peritoneal macrophages in vitro. These factors stimulate thymocytes from C3H/HeJ mice. Supernatants of peritoneal cell culture exhibiting this activity were fractionated by chromatographic procedures such as gel filtration and metal chelate affinity chromatography and the biological activities assayed. These fractionation studies indicate that several biologically active products occur in the supernatant. Four factors monokines (M) with different apparent molecular masses M1 (100,000), M2 (50,000), M3 (16,000) and M4 (7000) were obtained, one of which (M3) was identical to interleukin 1 (IL1). Several of the biochemical parameters of one of these factors, M2, were analyzed. It was found that this monokine had many properties in common with IL1: stimulation of proliferation of thymocytes from C3H/HeJ mice, similar amino acid composition and mobility during isoelectric focusing.

Amino Acids↗

Sympathetic activation on effort in patients with chronic heart failure. Long term effects of captopril.

Ten patients with congestive heart failure (CHF) (NYHA II-IV) on adjusted doses of digitalis and diuretics underwent a careful clinical assessment including an evaluation of exertion dyspnoea and the usual echocardiographic indices of cardiac performance. A cardiopulmonary exercise test with an increment of 20W every 3 minutes was prolonged until exhaustion. Systemic arterial pressure, ECG, VO2, VCO2 and VE were monitored throughout. Gas tensions, plasma catecholamines and lactate were measured in blood samples taken at the first and third minute of each exercise stage. The above measurements were carried out before and after 3 months of treatment with Captopril, 50 mg b.i.d. or t.i.d. A highly significant correlation between arterial lactate and plasma norepinephrine (NE) was observed in each patient during both exercise tests (r = 0.77 to 0.99; p less than 0.05 at least). Left ventricular end-diastolic dimensions were reduced by Captopril (from 69.9 +/- 1.7 to 65.2 +/- 1.4 mm, p less than 0.01) along with a concomitant increase in percent fractional shortening. Most of the patients were reclassified at a lower NYHA class and a significant decrease in dyspnoea score was observed. The exercise time was significantly increased (from 11.2 +/- 1.8 to 12.9 +/- 1.9 min; p less than 0.05), but the peak values of NE, arterial lactate and VO2 were not affected by the treatment. The predicted value of VE at a VCO2 of 1 L/min, regarded as an index of dyspnoea, was significantly decreased by Captopril (from 41.4 +/- 2.9 to 38.9 +/- 2.7 L/min; p less than 0.05). The positive effects of long-term treatment with Captopril on cardiac performance in CHF are confirmed. Sympathetic activity is linked to anaerobic muscular metabolism during exercise and seems to be independent of pharmacological ACE inhibition. The discrepancy between the exercise tolerance and the peak VO2 might be explained by a better utilization of the available energy.

Adult↗

[Purification of human plasma fibronectin by double affinity chromatography on gelatin and heparin-Trisacryl].

In this work the human plasma fibronectin was purified by affinity chromatography using a tandem column system. The first affinity column was filled with gelatin-Trisacryl whereas the second one contained heparin-Trisacryl. This double affinity chromatography demonstrated its high efficiency in term of purity and yield. Several analytical methods (electrophoresis, immunoelectrophoresis, F.P.L.C. and adhesion assay on cultured eucaryotic cells) evidenced in fact the high purity of the preparation as well as its biological behaviour in term of cell adhesion and spreading. The performances of the sorbents used facilitate the scaling up when large quantities of FNP are needed.

Acrylic Resins↗